The overall goal of this project is to understand the molecular and cellular changes underlying the aging process by studying two abnormal forms of aspartyl residues in the protein, namely, L-isoAsp and D-Asp, and protein carboxyl methlytransferase (PCMT), a putative enzyme which repairs these damaged residue. Specific aims are: (1) to measure the levels of protein bound L-isoAsp and D-Asp in particulate fraction of human and rodent brain proteins as a function of age; (2) to determine the methyl accepting capacities of brain praticulate fraction for PCMT; (3) to purity paired helical filaments from Alzheimer brain and determine the ratio of D-Asp/L-Asp in the filament as a function of age; (4) to purify calmodulin and synapsin-1 from early adult and aged human brains and compare their methyl-accepting capacities for PCMT; and (5) to determine the PCMT isozyme patterns in human and rat brain as a function of age.